A5025517447- Cell Adhesion Molecules Research
- Cellular Mechanics and Interactions
- Wnt/β-catenin signaling in development and cancer
- Monoclonal and Polyclonal Antibodies Research
- Cellular transport and secretion
- Cancer, Hypoxia, and Metabolism
- Protease and Inhibitor Mechanisms
- 3D Printing in Biomedical Research
- Developmental Biology and Gene Regulation
- Metabolism, Diabetes, and Cancer
- Epigenetics and DNA Methylation
- Cancer Research and Treatments
- Cancer Cells and Metastasis
- Extracellular vesicles in disease
- Microfluidic and Bio-sensing Technologies
- interferon and immune responses
- Retinal Development and Disorders
- Pancreatic function and diabetes
- RNA modifications and cancer
- Chemical Reactions and Isotopes
- Immune cells in cancer
- Axon Guidance and Neuronal Signaling
- Glycosylation and Glycoproteins Research
- Mathematical Biology Tumor Growth
- Cancer-related gene regulation
Inserm
2012-2024
Institut Cochin
2024
Institut Gustave Roussy
2020-2024
Cancer Research UK
2024
Cancer Research UK Scotland Institute
2017-2018
University of Glasgow
2017
University of Sheffield
2017
Université Paris-Sud
2012-2017
Laboratoire d'études sur les monothéismes
2012
The metalloprotease ADAM10/Kuzbanian catalyzes the ligand-dependent ectodomain shedding of Notch receptors and activates Notch. Here, we show that human tetraspanins evolutionary conserved TspanC8 subfamily (Tspan5, Tspan10, Tspan14, Tspan15, Tspan17, Tspan33) directly interact with ADAM10, regulate its exit from endoplasmic reticulum, four them ADAM10 surface expression levels. In an independent RNAi screen in Drosophila, two genes were identified as regulators. Functional analysis three...
Mutant p53s (mutp53) increase cancer invasiveness by upregulating Rab-coupling protein (RCP) and diacylglycerol kinase-α (DGKα)-dependent endosomal recycling. Here we report that mutp53-expressing tumour cells produce exosomes mediate intercellular transfer of mutp53's invasive/migratory gain-of-function increasing RCP-dependent integrin recycling in other cells. This process depends on ability to control production the sialomucin, podocalyxin, activity Rab35 GTPase which interacts with...
Abstract Formate overflow coupled to mitochondrial oxidative metabolism\ has been observed in cancer cell lines, but whether that takes place the tumor microenvironment is not known. Here we report observation of serine catabolism formate normal murine tissues, with a relative rate correlating levels and tissue state. Yet, increased transformed vivo models intestinal adenomas mammary carcinomas. The associated serum levels. Finally, show inhibition production by genetic interference reduces...
Abstract The role of glutaminolysis in providing metabolites to support tumour growth is well-established, but the involvement glutamine metabolism invasive processes yet be elucidated. Here we show that normal mammary epithelial cells consume glutamine, do not secrete glutamate. Indeed, low levels extracellular glutamate are necessary maintain homoeostasis, and provision drives disruption morphology promotes key characteristics phenotype such as lumen-filling basement membrane disruption....
Cell migration is essential to living organisms and deregulated in cancer. Single cell's ranges from traction-dependent mesenchymal motility contractility-driven propulsive amoeboid locomotion, but collective cell has only been described as a focal adhesion-dependent process. Here, we show that cancer clusters, patients lines, migrate without adhesions when confined into nonadhesive microfabricated channels. Clusters coordinate behave like giant super cells, mobilizing their actomyosin...
Abstract The Rab GTPase effector, Rab-coupling protein (RCP) is known to promote invasive behaviour in vitro by controlling integrin and receptor tyrosine kinase (RTK) trafficking, but how RCP influences metastasis vivo unclear. Here we identify an RTK of the Eph family, EphA2, be a cargo RCP-regulated endocytic pathway which controls cell:cell repulsion . Phosphorylation at Ser 435 Lemur kinase-3 (LMTK3) EphA2 897 Akt are both necessary Rab14-dependent (and Rab11-independent) trafficking...
Tspan5 is a member of subgroup tetraspanins referred to as TspanC8. These directly interact with the metalloprotease ADAM10, regulate its exit from endoplasmic reticulum and subsequent trafficking, differentially ability cleave various substrates activate Notch signaling. The study has been limited by lack good antibodies. This provides new insights into using monoclonal antibodies (mAbs), including two mAbs recognizing both highly similar tetraspanin Tspan17. Using these mAbs, we show that...
We have previously shown that Rab17, a small GTPase associated with epithelial polarity, is specifically suppressed by ERK2 (also known as MAPK1) signalling to promote an invasive phenotype. However, the mechanisms through which Rab17 loss permits invasiveness, and endosomal cargoes are responsible for mediating this, unknown. Using quantitative mass spectrometry-based proteomics, we found knockdown of leads highly selective reduction in cellular levels v-SNARE (Vamp8). Moreover, proteomics...
Abstract Altered cellular metabolism has been associated with acquisition of invasive phenotypes during metastasis. To study this, we combined a genetically engineered mouse model mammary carcinoma syngeneic transplantation and primary tumour resection to generate isogenic cells from tumours their corresponding lung micrometastases. Metabolic analyses indicated that micrometastatic increase proline production at the expense glutathione synthesis leading reduction in total levels....
When an invading cancer cell attempts to pass through a hole in the extracellular matrix (ECM) which is too small for its nucleus, this generates physical tension. This tension sensed by nucleus–centrosome connection that activates trafficking of endosomal vesicles containing metalloprotease, MT1-MMP1 site constraint. Recent evidence shows how focussed ECM degradation relieves constraint and allows cells continue invading.
The regulation of integrin function is key to fundamental cellular processes, including cell migration and extracellular matrix (ECM) assembly. In this issue, Georgiadou et al. (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201609066) report that the metabolic sensor adenosine monophosphate–activated protein kinase influences tensin production regulate α5β1-integrin fibrillar adhesion assembly thus reveal an important connection between energy metabolism ECM
Abstract Cell migration is essential to most living organisms. Single cell involves two distinct mechanisms, either a focal adhesion- and traction-dependent mesenchymal motility or an adhesion-independent but contractility-driven propulsive amoeboid locomotion. Cohesive of group cells, also called collective migration, has been only described as mode locomotion where the driving forces are mostly exerted at front by leader cells. Here, studying primary cancer specimens lines from colorectal...
Colorectal cancer (CRC) is the second cause of cancer-related death where CpG-island methylation pathways (CIMP) associated to KRAS/BRAF mutations, two oncogenes rewiring cell metabolism, worst prognosis and resistance classical chemotherapies. Despite this, question a possible metabolic in CIMPs has never been asked. Here we asked if dysregulations were status tumours by evaluating transcriptome CRC tumours. CIMP-high patients found present hyper-metabolism activating mainly carbohydrates,...
Colorectal cancer (CRC) is the second cause of cancer-related death; CpG-island methylation pathway (CIMP) associated with KRAS/BRAF mutations, two oncogenes rewiring cell metabolism, worse prognosis, and resistance to classical chemotherapies. Despite this, question a possible metabolic in CIMPs has never been investigated. Here, we analyse whether dysregulations are tumour by evaluating transcriptome CRC tumours. CIMP-high patients were found present hypermetabolism, activating mainly...
Summary Understanding the mechanisms that facilitate early events in metastatic seeding is key to developing therapeutic approaches reduce metastasis – leading cause of cancer-related death. Using whole animal screens genetically engineered mouse models cancer we have identified circulating metabolites associated with metastasis. Specifically, highlight pyrimidine uracil as a prominent metastasis-associated metabolite. Uracil generated by neutrophils expressing enzyme uridine phosphorylase-1...
Abstract Glutamine metabolism is well-established to contribute cancer cell growth and proliferation by providing a source of nitrogen for nucleotide amino acid biosynthesis as well TCA cycle intermediates. There also accumulating evidence that glutamine may metastasis although mechanistic links tumour migration invasion remain unclear. We have generated number highly invasive primary lines from the polyoma middle-T genetically engineered mouse model breast (MMTV-PyMT) found withdrawal these...